Home-based EXergames To impRove cognitivE Function in MUltiple Sclerosis

Study design: Phase II, multicenter, randomized, sham-controlled, single-blind, parallel arm, multicenter study to test the hypothesis that home-based exergames is not inferior to home-based cognitive rehabilitation delivered by a software application (app) for mobile devices and both interventions are superior to a placebo-analogue cognitive intervention in improving cognitive function and reducing cognitive-motor interference in people with multiple sclerosis (MS).

Procedures: Participants will be randomized in a 1:1:1 ratio to receive an 8-week home-based training with exergames (intervention of interest) or adaptive COGNI-TRAcK (comparator intervention) or sham COGNI-TRAcK (placebo-analogue intervention). Study assessment will be done at study enrolment (baseline), at the end of the 8-week intervention period (immediate post-training, Week 8) and after 16 weeks from randomization (post-training follow-up, Week 16).

Investigational interventions:

1. Exergames: home-based repetition of several games delivered by the Nintendo © Wii Balance Board, a commercial off-the-shelf video game console for re-training of balance and postural strategies

2. Adaptive COGNI-TRAcK: adaptive (i.e. automatic adjustment of tasks difficulty) working memory training delivered by a customized application software for mobile devices to self-administer at-home

3. Sham COGNI-TRAcK: non-adaptive (i.e. constant difficulty level) working memory training delivered by the same app as afore described

Primary endpoint: changes at the Symbol Digit Modalities Test (SDMT), a measure of sustained attention and information processing speed.

Secondary endpoint: changes at the BICAMS (z-scores), a brief, practical and universal assessment tool for cognitive impairment in MS.

Additional endpoints: magnitude of cognitive-motor interference estimated as dual-task cost of balance and walking.

Sample size estimation: The investigators estimated a pre-defined 8-point non-inferiority margin, based on a significant effect of the COGNI-TRAcK in inducing an about 8-point mean increase at SDMT score (with respect to a sham intervention). Accordingly, 35 participants per arm are required to ensure, with an approximately 85%-power level, that the lower limit of a one-side 95% confidence interval will be above the pre-defined non-inferiority margin. Therefore, considering also a drop-out rate of 25%, a total of 132 subjects should be enrolled.